Forgot your Password

If you have forgotten your password, please enter your account email below and we will reset your password and email you the new password.


Login to SciCrunch


Register an Account

Delete Saved Search

Are you sure you want to delete this saved search?


NIF LinkOut Portal


MUC1 oncoprotein blocks nuclear targeting of c-Abl in the apoptotic response to DNA damage.

Raina D, Ahmad R, Kumar S, Ren J, Yoshida K, Kharbanda S, Kufe D
The EMBO journal


The nonreceptor c-Abl tyrosine kinase binds to cytosolic 14-3-3 proteins and is targeted to the nucleus in the apoptotic response to DNA damage. The MUC1 oncoprotein is overexpressed by most human carcinomas and blocks the induction of apoptosis by genotoxic agents. Using human carcinoma cells with gain and loss of MUC1 function, we show that nuclear targeting of c-Abl by DNA damage is abrogated by a MUC1-dependent mechanism. The results demonstrate that c-Abl phosphorylates MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the c-Abl SH2 domain to the pTyr-60 site. Binding of MUC1 to c-Abl attenuates phosphorylation of c-Abl on Thr-735 and the interaction between c-Abl and cytosolic 14-3-3. We also show that expression of MUC1 with a mutation at Tyr-60 (i) disrupts the interaction between MUC1 and c-Abl, (ii) relieves the MUC1-induced block of c-Abl phosphorylation on Thr-735 and binding to 14-3-3, and (iii) attenuates the MUC1 antiapoptotic function. These findings indicate that MUC1 sequesters c-Abl in the cytoplasm and thereby inhibits apoptosis in the response to genotoxic anticancer agents.

  1. Welcome

    Welcome to NIF. Explore available research resources: data, tools and materials, from across the web

  2. Community Resources

    Search for resources specially selected for NIF community

  3. More Resources

    Search across hundreds of additional biomedical databases

  4. Literature

    Search Pub Med abstracts and full text from PubMed Central

  5. Insert your Query

    Enter your search terms here and hit return. Search results for the selected tab will be returned.

  6. Join the Community

    Click here to login or register and join this community.

  7. Categories

    Narrow your search by selecting a category. For additional help in searching, view our tutorials.

  8. Query Info

    Displays the total number of search results. Provides additional information on search terms, e.g., automated query expansions, and any included categories or facets. Expansions, filters and facets can be removed by clicking on the X. Clicking on the + restores them.

  9. Search Results

    Displays individual records and a brief description. Click on the icons below each record to explore additional display options.